1. Field of the Invention
The present invention relates to the use of a new automated method which measures and regulates pressure and flow in the spinal canal in order to characterize individual patients' cerebrospinal fluid (CSF) dynamics. To accomplish this, a unique disposable tube-set plate with computer regulated solenoid pinch valves to control flow pressure and a new location of small pressure sensors allows for fully automatic control of the system.
2. Description of the Related Art
Hydrocephalus is a condition affecting people who are unable to properly regulate their cerebrospinal fluid circulation. Cerebrospinal fluid (CSF) produced by the ventricular system is normally absorbed by the venous system. In a person suffering from hydrocephalus, the cerebrospinal fluid is not absorbed in this manner, but instead accumulates in the ventricles (free spaces) of the patient's brain. Normal pressure hydrocephalus (NPH) refers to a condition of pathologically enlarged ventricular size with normal pressures on lumbar puncture. If left untreated, an increasing volume of fluid can elevate the patient's intracranial pressure and can lead to serious medical conditions such as compression of the brain tissue and impaired blood flow to the brain.
The earliest description of hydrocephalus has been ascribed to Hippocrates (466-377 BC), who pointed out symptoms such as headache, vomiting and visual disturbance. Claudius Galen of Pergamon (130-200 AD) and medieval Arabian physicians also described hydrocephalus, believed to be due to an extracerebral accumulation of water.
Surgery to reduce fluid accumulation in the cerebrospinal fluid system was first performed by Le Cat in 1744, but it was not until the late nineteenth century, when sufficient pathophysiological knowledge and aseptic conditions were gained, that surgical procedures were truly introduced to treat hydrocephalus. In the 1960s, silicone and the invention of artificial valves led to a therapeutic breakthrough. With the development of an implantable shunt system to divert excess fluid, hydrocephalus went from being a fatal disease to becoming curable (Aschoff A, et al. The scientific history of hydrocephalus and its treatment. Neurosurg Rev 22:67-93; discussion 94-5, 1999). In 1965, Hakim and Adams described the newly discovered category of patients with normal cerebrospinal fluid pressure appearing to suffer from hydrocephalus, who benefited from shunt surgery (Hakim S and Adams R D. The special clinical problem of symptomatic hydrocephalus with normal cerebrospinal fluid pressure. Observations on cerebrospinal fluid hydrodynamics. J Neurol Sci 2:307-27, 1965). The syndrome was named normal pressure hydrocephalus (NPH), and since then extensive work has been put into finding and developing new methods to identify those patients with NPH who will improve from shunt implantation surgery. Today, ventricular shunting is one of the most commonly performed neurosurgical procedures, including for communicating and non-communicating hydrocephalus as well as shunt malformation. The annual incidence of operations varied between regional clinics from 2.3 to 6.3 per 100,000 inhabitants (Tisell M, et al. National and regional incidence of surgery for adult hydrocephalus in Sweden. Acta Neurol Scand 2005 August; 112(2):72-5).
Shunting has dramatically changed the prognosis of people with hydrocephalus, many of them benefiting from normal life expectancies and regaining their baseline intelligence. The use of shunts, however, has created many unique problems of shunt dependence with frequent shunt revisions being the rule for most hydrocephalic patients. Shunt complications assume a major amount of all neurosurgeons' efforts.
CSF shunt implantation surgery involves establishing an accessory pathway for the flow of CSF in order to bypass an obstruction of the natural pathways. The shunt is positioned to enable the CSF to be drained from the cerebral ventricles or subarachnoid spaces into another absorption site, such as the right atrium of the heart or the peritoneal cavity, via a system of small tubes known as catheters. A regulatory device (known as a valve) can be inserted into the pathway of the catheters in order to regulate flow of CSF, depending on the pressure. This drainage enables the excess CSF within the brain to be evacuated and thereby, the pressure within the cranium to be reduced.
The currently accepted means of measuring pressure and flow dynamics of CSF is a two-part clinical exam, known as the lumbar infusion test and CSF tap test. These tests are limited in that they do not allow for standardization for the measurement and regulation of pressure and flow of CSF, and require manual adjustment throughout the examination. The infusion test investigates the dynamics of the CSF system, and since the shunt treatment of IAHS involves imposing a change on the CSF dynamical system, it is natural to look at the function of the system before treatment. The infusion test determines the patient's intracranial pressure (ICP) at rest, and the conductance to CSF outflow (Cout, inverse of outflow resistance, Rout). The infusion test can also be used to determine shunt function in patients on whom there has already been an operation. A problem with the infusion test is that it is carried out, analyzed and interpreted in different ways at different investigating centers. Some of the most common methods used to determine Cout (or Rout) include Katzman's constant rate infusion test with various modifications, the bolus injection and servo-controlled constant pressure infusion. Although the bolus test is known to produce a higher Cout than the other methods they all claim clinical utility but with different Cout threshold levels. There is a lack of consensus concerning the usefulness of Cout as a predictor for shunt surgery, with a large number of studies supporting it but many as well not finding the parameter useful in the selection process A challenge with this type of measurement is that the physiological periodic variations in ICP, related to vasogenic volume variations in the craniospinal system, often are large and the net infusion flow is small. This can be viewed as a low signal to noise ratio. Also, the magnitude of the variations differs greatly between patients. This will affect each individual infusion test in such a way that the results obtained from a patient with small variations, will be more reliable than those from a patient with larger variations. None of the methods currently in use for performing infusion tests give any numerical feedback, on a display or in printout form or the like, to the user concerning the reliability of individual investigations. Consequently, all Cout values are considered equally reliable, regardless of their physiological background. Based on such data the analysis and the interpretation of individual Cout values are difficult, and the lack of consensus concerning the usefulness of Cout as a predictor might be a consequence of the unknown uncertainty of individual infusion tests. One of the major benefits of the automated tube-set invention herein is the flexibility of the system, in that the user can combine these different components (constant pressure, constant flow, or bolus injection) to attain the desired measurement.
Using the prior machine invention (WO 2006/091164), which systematically generates or provides pressure and flow information, the hydrodynamic parameters of a patient are determined in order to confirm diagnosis of hydrocephalus. In particular, this prior machine for determining the hydrodynamic properties of the fluid system surrounding the brain and the spinal cord comprises a hose pump for infusion of artificial cerebrospinal fluid for example Ringer's acetate, a pump hose, pressure transducers for continuous registration of the intracranial pressure, an invasive contact object for creating fluid contact with the cerebrospinal fluid system and a computer with software for computerized collection and analysis as well as control of pump speed, characterized in that a calculation unit, forming part of said software, is designed to be controlled thereby using an adaptive method which at each pressure-flow level considers the time of measure and the patients fluctuations in physiologic signals for calculating, in real time, when the relation between measure time and measure accuracy in pressure and flow on the actual level is sufficient, that said software is designed for, when said relation between measure time and measure accuracy on the actual level is sufficient, initiating the next pressure-flow level according to a predetermined protocol, and that for real-time analysis, said software is designed for, from the pressure-flow information from the investigation, determining and giving an account of the patient's hydrodynamic parameters with an uncertainty estimate. In conjunction with this machine, a new disposable and fully automated tube-set of the invention herein, can be used for more accurate, simple, fully automatic, and sterile measurements of the pressure and flow dynamics of CSF.
The earlier version of the apparatus mentioned above, for performing standardized and semi-automated infusion tests was developed by Sundström in WO 2006/091164. The apparatus was PC-based with a user interface consisting of a computer screen and a track ball (see FIG. 1 of WO 2006/091164). It also included an electronic control unit, two pressure transducers (PMSET 1TNF-R, BD Critical Care Systems Pte Ltd, Singapore), a peristaltic pump (Reglo-Analog-E, MS/CA1-E/12-160, Ismatec, Switzerland), a bottle holder for artificial CSF, an emergency stop and a set of tubing. Data collection and communication between software and hardware were performed using two data acquisition cards, PCI-MIO-16XE-50 and PCI-6503 (National Instruments, Inc., Austin, Tex., USA). The electronic control unit included pressure amplifiers, analogue safety checks that stop the pump at dangerously high or low ICP, and a signal to ensure communication with the PC. A built-in horizontal laser line was used for zero level alignment of the equipment in relation to the patient. The components were mounted on an electrically maneuvered pillar and the pillar was mounted on wheels to make the system mobile.
The use of the invention herein, the automated tube-set, improves prior methods of gathering these measurements. Previously, pressure flow levels were set manually in the beginning and at the end of the examination period via eight adjustable valves. Instead of using manually adjustable stopcocks of the semi-automated system, the invention herein has automatic magnetic solenoid pinch valves that are regulated using computer software. This means that the automated tube-set is not subject to operator variability and thus the invention herein is safer for the patient than previous methods. This renders the entire analysis process of measuring pressure and flow dynamics of CSF automatic.
The invention herein is much easier and faster for the operator to mount than prior methods. With the previous tube-set, the user had to know how to connect approximately eight different parts, while in the present invention, the plate needs only to be snapped on to the instrument for mounting.
In addition, the time needed to acquire exact measurements has not been known or standardized in prior techniques, whereas the automated tube-set eliminates this variable by adjusting automatically to the patient from the beginning to the end of the exam. Another advantage of the automated tube-set technology herein is that people of various training levels can use it, since it is a fully automated method. This improves simplicity and thereby, accuracy of the results. At the same time, accuracy and simplicity also improve with a closer sensor location to the tube and the patient, without the need to draw fluid into the machine. The unit is also disposable, which means it is easy to keep sterile and safe for each individual patient. The location of a new and smaller pressure sensor directly on the disposable tube-set also improves issues of sterility.
Similar technology i.e. a tube-set on a plate or cassette is found in peristaltic pump devices, which have been widely used for life support during open-heart surgery and dialysis over the last few decades. In a peristaltic pump, a piece of tubing is compressed in a forward motion with the tube acting both as a check valve and as a transport mechanism. A peristaltic pump is used principally for pumping blood products. Typically, a peristaltic pump has a rotor with two rollers, which squeeze the tube up against a circular tube track. The tube-set plate of the invention herein differs from the earlier tube-set technology in for example, that the tube-set of the invention is regulated by automatic valves that open and close according to pressure flow parameters. The pressure flow translates the pressure of the CSF into an electronic signal, which yields a measurement of the results.
In U.S. Pat. No. 6,531,061, a dialysis cassette is assembled by the combination of a first and second flexible polymeric sheet bonded together to form a semi-rigid frame. It is a disposable dialysis cassette that is flat, flexible, self-closing and applicable to solutions containing proteins, DNA, RNA, or other molecules. The dialysis cassette embodies a first and second semi-permeable dialysis membrane, or tubular dialysis membrane, sealed by a flexible frame to form a dialysis chamber having a self-closing channel for the introduction of a dialysis sample by either a pipette or other dispensing mechanism. However, this system does not open automatically as the invention herein, and functions on an osmotic gradient rather than a pressure flow parameter.
In U.S. Patent Publication No. 2007/0217933, for a tubing cassette for a peristaltic pump, a hose cartridge is provided for a peristaltic pump comprising a cartridge housing, including a flexible pump hose segment extending through the cartridge housing. Both ends of the pump hose segment are fixed in the cartridge housing by means of a first fixing member and of a second fixing member arranged in the area of a first front face of the cartridge housing. The cartridge housing comprises a recess for the engagement of a roller wheel of the pump in the interior of the cartridge housing. In this case, the fluid is transported via the hose pump, rather than the automated pressure flow parameters of the patient as described by the invention herein.
It is an object of the invention to provide an improved and simplified method of fully automating the measurement of CSF pressure and flow dynamics by using a disposable tube-set plate. Other objects and advantages will be more fully apparent from the following disclosure.